EP1899356A1 - Procede de preparation du cefdinir - Google Patents

Procede de preparation du cefdinir

Info

Publication number
EP1899356A1
EP1899356A1 EP05760572A EP05760572A EP1899356A1 EP 1899356 A1 EP1899356 A1 EP 1899356A1 EP 05760572 A EP05760572 A EP 05760572A EP 05760572 A EP05760572 A EP 05760572A EP 1899356 A1 EP1899356 A1 EP 1899356A1
Authority
EP
European Patent Office
Prior art keywords
cefdinir
minutes
stirred
contents
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05760572A
Other languages
German (de)
English (en)
Inventor
Bandi Parthasaradhi Reddy
Kura Hetero Drugs Limited RATHNAKAR REDDY (R&D)
rapolu Hetero Drugs Limited RAJI REDDY (R&D)
Dasari Hetero Drugs Ltd. R&D MURALIDHARA REDDY
Nagabelli Hetero Drugs Limited MURALI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hetero Drugs Ltd
Original Assignee
Hetero Drugs Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hetero Drugs Ltd filed Critical Hetero Drugs Ltd
Publication of EP1899356A1 publication Critical patent/EP1899356A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring

Definitions

  • the present invention provides an improved process for the preparation of high assayed cefdinir. BACKGROUND OF THE INVENTION
  • cefdinir is obtained as amorphous solid.
  • Various processes for preparing cefdinir are described in PCT Publication No. WO 2004/016623 A1, PCT Publication No. WO 2002/098884 A1 and U.S. Patent No. 6,350,869 B1.
  • purified cefdinir is prepared by treating a solution of 7-[2-(2-aminothiazol-4-yl)-2-(methylcarbonyl oxyimino)acetamido]-3-vinyl-cephem-4-carboxylic acid in the form of salt, with p- toluenesulfonic acid, in methanol with concentrated sulfuric acid at or less than 1O 0 C, adding aqueous sodium carbonate solution to adjust the pH to 5.0; subjecting the solution to carbon treatment and adjusting the pH of the filtrate to 3.0 with sulfuric acid solution to obtain cefdinir.
  • cefdinir is prepared by treating p-TsOH.2DMAC salt of 7 ⁇ -[(Z)-2-(2-aminothiazol-4-yl)-2- trityIoxyiminoacetamido]-3-vinyl-3-cephem-4-carboxyIic acid with formic acid and sulfuric acid to obtain pure cefdinir.
  • Cefdinir obtained by these processes has an important draw back of the being less assayed.
  • U.S. Patent No. 6,350,869 B1 disclosed that cefdinir can form stable salt with dicyclohexylamine.
  • crude cefdinir can be purified by converting the crude cefdinir into cefdinir dicyclohexylamine salt, crystallizing pure cefdinir dicyclohexylamine salt, liberating the cefdinir from the salt by adding an acid and crystallizing pure cefdinir.
  • the product obtained as above is high assayed cefdinir, the process is lengthy involving the additional steps of isolating salts such as dicyclohexylamine salt of cefdinir as crystalline solid as intermediates.
  • the high assayed cefdinir may be obtained by operationally convenient manner just by controlling temperature.
  • a process for preparing high assayed cefdinir which comprises: a) stirring an aqueous solution of a crude acid addition salt of cefdinir for at least about 3 minutes at -5 to +5 0 C; b) raising the temperature to about 33 - 4O 0 C and stirring for at least about 10 minutes at about 33 - 4O 0 C; c) filtering the solution through hiflo bed at 25 - 4O 0 G; d) adjusting the pH of the filtrate obtained to isoelectric point of cefdinir at 20 - 3O 0 C with a base to precipitate cefdinir from the solution; and e) filtering or centrifuging the solid precipitated to obtain high assayed cefdinir.
  • Preferable acid addition salts are hydrochloric acid, phosphoric acid, sulfuric acid and methanesulfonic acid salt of cefdinir, more
  • Crude cefdinir refers to cefdinir for which further treatment is required to obtain high assayed cefdinir.
  • High assayed cefdinir refers to cefdinir having the assay of not less than 95%, preferably between 96 and 101%.
  • cefdinir is determined by a suitable High Performance
  • Liquid Chromatograph consisting of a pump an UV - VIS detector, sample injector, controller and integrator or equivalent software.
  • the system is equipped with Ci 8 5 ⁇ m 4.6 x 150 mm column (Inertial ODS 3 is suitable).
  • Assay of cefdinir is performed by setting HPLC parameters like UV wavelength 247 nm, flow rate of about 1.0 ml/min., column temperature at about 30 + 2 0 C, and using
  • the aqueous solution of crude acid addition salt of cefdinir used in step- (a) may be prepared, for example, by treating crude cefdinir with an acid in water medium or by dissolving crude acid addition salt of cefdinir in water.
  • the aqueous solution of crude acid addition salt of cefdinir may also be prepared by converting a sodium or potassium salt of cefdinir into corresponding crude acid addition salt of cefdinir by a conventional method in aqueous medium.
  • the aqueous solution is stirred preferably for 3 to 30 minutes, more preferably for 3 to 15 minutes at -5 to +5 0 C. .
  • the temperature of the contents in step-(b) is raised to about 33 - 40 0 C, preferably to about 35 - 4O 0 C and stirred for at least about 10 minutes, preferably for 10 minutes to 1 hour, more preferably for 10 minutes to 30 minutes at about 33 - 4O 0 C, and preferably at about 35 - 4O 0 C.
  • step-(c) The contents are then filtered in step-(c) through hiflo bed at 25 - 4O 0 C, preferably at 33 - 4O 0 C and more preferably at 35 - 40 0 C.
  • the contents obtained in step-(b) may be subjected to carbon treatment before step- (c) is carried out.
  • step d The pH of the filtrate obtained in step-(c) is adjusted to isoelectric point (step d) at about 20 - 3O 0 C with a base such as sodium bicarbonate or sodium carbonate to precipitate cefdinir from the solution.
  • a base such as sodium bicarbonate or sodium carbonate
  • the precipitated cefdinir is collected by filtration or centrifugation (step e) to obtain high assayed cefdinir.
  • 2-Amino-alpha-(acetyloxyimino)-4-thiazole acetic acid (76 gm) is added to methylene chloride (1150 ml) at 25 - 35 0 C, distilled to collect 30 ml of methylene chloride at 4O 0 C, refluxed for 30 minutes at 4O 0 C and again distilled to collect 110 ml of methylene chloride. Then the reaction mass is cooled to 15 0 C, bis[thio(benzothiazole)] (167 gm) and triphenyl phosphine (137.3 gm) are added for 5 minutes at 15 0 C and stirred for 10 minutes at the same temperature.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

La présente invention concerne un procédé amélioré pour la préparation du cefdinir en concentration élevée. Ainsi, du cefdinir brut est ajouté à de l'eau chauffée entre 25 et 30 °C, puis de l'acide chlorhydrique à 18 % est lentement ajouté de manière à former une solution claire. La solution est refroidie à -5 °C puis agitée pendant 5 minutes à une température allant de -5 °C à +5 °C. Ensuite, la température de la masse est augmentée pour atteindre 35 à 38 °C, puis elle est agitée pendant 15 minutes à la même température. Du carbone eno est ajouté à la masse de réaction à une température comprise entre 35 et 38 °C, puis agité pendant 30 minutes à une température allant de 35 à 38 °C. Le contenu est ensuite filtré sur un lit hiflo et lavé à l'eau. Le filtrat est ensuite refroidi à 25 °C et le pH est réglé par progression lente à 2,6 avec une solution saturée de bicarbonate de sodium, puis agité pendant 60 minutes à une température allant de 25 à 30 °C. Le cefdinir en concentration élevée s'obtient une fois le solide filtré, lavé à l'eau et séché sous vide à 40 °C.
EP05760572A 2005-06-15 2005-06-15 Procede de preparation du cefdinir Withdrawn EP1899356A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2005/000199 WO2006134607A1 (fr) 2005-06-15 2005-06-15 Procede de preparation du cefdinir

Publications (1)

Publication Number Publication Date
EP1899356A1 true EP1899356A1 (fr) 2008-03-19

Family

ID=37531992

Family Applications (1)

Application Number Title Priority Date Filing Date
EP05760572A Withdrawn EP1899356A1 (fr) 2005-06-15 2005-06-15 Procede de preparation du cefdinir

Country Status (3)

Country Link
US (1) US20080287673A1 (fr)
EP (1) EP1899356A1 (fr)
WO (1) WO2006134607A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050087776A (ko) 2002-08-13 2005-08-31 산도즈 아게 세프디니르 중간체
JP2008524265A (ja) * 2005-10-31 2008-07-10 テバ ファーマシューティカル インダストリーズ リミティド セフジニルの製造方法
EP1828208A2 (fr) * 2005-10-31 2007-09-05 Teva Pharmaceutical Industries Ltd Formes cristalline du sel de cesium de cefdinir
CN102516261A (zh) * 2011-12-20 2012-06-27 浙江国邦药业有限公司 一种头孢地尼的制备方法
CN104447794A (zh) * 2014-11-18 2015-03-25 成都医路康医学技术服务有限公司 一种头孢地尼的制备方法
WO2019060171A1 (fr) * 2017-09-20 2019-03-28 Calista Capital, Llc Procédé pour l'arrêt du tabac
CN113214186A (zh) * 2021-05-18 2021-08-06 山东昌邑四方医药化工有限公司 头孢地尼活性酯的精制方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004104010A1 (fr) * 2003-05-20 2004-12-02 Ranbaxy Laboratories Limited Forme cristalline de cefdinir

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8323034D0 (en) * 1983-08-26 1983-09-28 Fujisawo Pharmaceutical Co Ltd 7-substituted-3-vinyl-3-cephem compounds
AT405283B (de) * 1997-04-04 1999-06-25 Biochemie Gmbh Neues kristallines 7-(z)-(2-(2-aminothiazol-4-yl) -2-hydroxyiminoacetamido)-3-vinyl-3-cephem-4- carbonsäure dicyclohexylammoniumsalz und verfahren zu dessen herstellung
US6721352B2 (en) * 2002-08-06 2004-04-13 Scientific-Atlanta, Inc. Method and device for detecting the presence of a carrier signal transmitted in the reverse RF path
ITMI20022724A1 (it) * 2002-12-20 2004-06-21 Antibioticos Spa Sali cristallini del cefdinir.
US20050059819A1 (en) * 2003-09-12 2005-03-17 Duerst Richard W. Cefdinir pyridine salt
US7741478B2 (en) * 2004-07-05 2010-06-22 Orchid Chemicals & Pharmaceuticals Limited Salts in the preparation of cephalosporin antibiotics
JP2008524265A (ja) * 2005-10-31 2008-07-10 テバ ファーマシューティカル インダストリーズ リミティド セフジニルの製造方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004104010A1 (fr) * 2003-05-20 2004-12-02 Ranbaxy Laboratories Limited Forme cristalline de cefdinir

Also Published As

Publication number Publication date
US20080287673A1 (en) 2008-11-20
WO2006134607A1 (fr) 2006-12-21

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